COVID-19 has different clinical stages, and effective therapy depends on the location and extent of the infection. The purpose of this review is to provide a background for understanding the progression of the disease throughout the pulmonary epithelium and discuss therapeutic options. The prime sites for infection that will be contrasted in this review are the conducting airways and the gas exchange portions of the lung. These two sites are characterised by distinct cellular composition and innate immune responses, which suggests the use of distinct therapeutic agents. In the nose, ciliated cells are the primary target cells for SARS-CoV-2 viral infection, replication and release. Infected cells shed their cilia, which disables mucociliary clearance. Evidence further points to a suppressed or incompletely activated innate immune response to SARS-CoV-2 infection in the upper airways. Asymptomatic individuals can still have a productive viral infection and infect others. In the gas exchange portion of the lung, the alveolar type II epithelial cell is the main target cell type. Cell death and marked innate immune response during infection likely contribute to alveolar damage and resultant acute respiratory distress syndrome. Alveolar infection can precipitate a hyperinflammatory state, which is the target of many therapies in severe COVID-19. Disease resolution in the lung is variable and may include scaring and long-term sequalae because the alveolar type II cells are also progenitor cells for the alveolar epithelium.
- airway epithelium
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JPB and EKV are joint first authors.
Contributors JPB: wrote and approved the manuscript. EKV: wrote and approved the manuscript. HH: edited and approved the manuscript. RJM: wrote and approved the manuscript.
Funding The authors are supported in part from funds from the National Institutes of Health (HL131634 JPB), Cystic Fibrosis Foundation (EKV), and NeuroRx corporation (JPB and RJM). EKV is a Boettcher Early Career Investigator.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.